Parkinson's disease is a neurological disorder characterized by a decrease of voluntary movements. The afflicted patient has reduction of motor activity and slower voluntary movements compared to the normal individual. He has characteristic "mask" face, a tendency to hurry while walking, bent over posture and generalized weakness of the muscles. There is a typical "leadpipe" rigidity of passive movements. Another important feature of the disease is the tremor of the extremities occurring at rest and decreasing during movements.
Parkinson's disease, the etiology of which is unknown, belongs to a group of the most common movement disorders named parkinsonism, which affects approximately one person per one thousand. These other disorders grouped under the name of parkinsonism may result from viral infection, syphilis, arteriosclerosis and trauma and exposure to toxic chemicals and narcotics.
Regardless of the cause of the disease, the main pathologic feature is degeneration of dopaminergic cells in basal ganglia, especially in substantia nigra. Due to premature death of the dopamine containing neurons in substantia nigra, the largest structure of the basal ganglia, the striatum, will have reduced input from substantia nigra resulting in decreased dopamine release. The understanding of the underlying pathology led to the introduction of the first successful treatment which can alleviate Parkinson's disease. Virtually all approaches to the therapy of the disease are based on dopamine replacement. Drugs currently used in the treatment can be converted into dopamine after crossing the blood brain barrier, or they can boost the synthesis of dopamine and reduce its breakdown. Unfortunately, the main pathologic event, degeneration of the cells in substantia nigra, is not helped. The disease continues to progress and frequently after a certain length of time, dopamine replacement treatment will lose its effectiveness.
The treatment representing this invention is based on a different principle: the reducing of degeneration of the cells and promoting healing in substantia nigra.
The human body has remarkable potential for regeneration. When the body incurs damage to the tissue, there is an immediate rise of new cells which replace those that were damaged. Unfortunately, in the adult human brain, the dead neurons are not replaced. The basic dogma in neuroscience is that once the adult set of neurons has been produced, no stem cells persist to generate new neurons. Such rule applied for both vertebrates and invertebrates. Recent studies of Nottebohm et al. seem to challenge this dogma by proving that the occurrence of new neurons can continue in the brain of the adult bird (Alvarez-Buylla and Nottebohm, Nature, 335:353 (1988)). During the development, the cells are undergoing a process of differentiation. After they reach terminal differentiation, they will remain viable for a long time, but they won't be able to proliferate. In order to survive, these cells will need a continuous supply of growth factors (Seshadri and Campisi, Science, 247:205 (1990)). The availability of certain growth factors will determine whether neurons will live shorter or longer lives. Nerve growth factor is the best characterized polypeptide growth factor in the nervous system (Levi-Montalcini and Angeletti, Physiol. Rev., 48:534 (1968)). Recently, the additional polypeptide growth factors active in the nervous system have been described: brain-derived neurotrophic factor and neurotrophin-3 (Leibrock et al., Nature, 341:149 (1989); Maisonpierre et al., Science, 247:1446 (1990)). It has been postulated that these polypeptide factors can be used in overcoming neuronal degeneration, but they have not been used as yet with success in the treatment of Parkinson's disease.
Antineoplastons are differentiation inducing peptides and amino acid derivatives, which were first described by S. R. Burzynski (Burzynski, U.S. Pat. No. 4,470,970; Burzynski, Drugs Exptl. Clin. Res. Suppl. 1, 12:l (1986)). Interestingly, Antineoplastons inhibit neoplastic growth, and at the same time stimulate normal cell growth (Burzynski, Physiol. Chem. Phys., 8:275 (1976)). During clinical applications, Antineoplastons A2 and A5 have shown prominent stimulation of the growth of the cells of ectodermal origin, such as epidermis (Burzynski, Drugs Exptl. Clin. Res. Suppl. 1, 13:1 (1987) and 13:1, 37 (1987)). In the human body, the nervous system develops from the cells of the neural tube and the neural crest, which originate from the ectoderm. Initial observation of the stimulatory effect of Antineoplastons on the cells from ectodermal origin helped to introduce the hypothesis that Antineoplastons may also have a stimulatory effect on the cells of the central nervous system, which will extend survival of these cells. The increased survival of the cells in substantia nigra may improve the symptoms of Parkinson's disease and possibly arrest the progression of the disease.